Evidence Based Case Report

SERUM PROCALCITONIN FOR

DIFFERENTIATING BACTERIAL INFECTION
FROM DISEASE FLARES IN PATIENTS WITH
SYSTEMIC LUPUS ERYTHEMATOSUS
Evie Rosa Widyawanti N

INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with
clinical features of multi-system damages and infection is one of the major
causes of death.
Increased risk of infection due to intrinsic disturbances of immune responses
and the use of immunosuppressive drugs.
Infections may mimic exacerbations of SLE, leading to confusion over the
diagnosis and appropriate treatment.
A reliable biomarker that provides high sensitivity and specificity for the early
discrimination of bacterial infection from disease flare in patients with
autoimmune diseases was needed.

CLINICAL SCENARIO

Physical
Examinatio
n

BP :130/90 mmHg, HR: 120 bpm, RR: 36 tpm and T: 38.5 0C.
Anemic conjunctiva, JVP was 5+2 H2O
Chest examination revealed decreased vesicular sound on right lung
with crackle both of lung.
Pitting edema on both legs

Lab Results

Hb of 8.7 g/dl (normocytic normochromic anemia) ,Ht: 25.2, WBC:

18.700/l, Dif Count : 0/0/89/6/3/2 , PLT: 258000/l, ANA positive, C3
and C4= 57 mg/dl and 13 mg/dl, Ur and Cr =179.2 mg/dl and 5.77
mg/dl.

A 30 year old female came with progressive shortness of breath 3 days

prior to admission that was continuous and aggravated by physical
activities.
She also had high fever and productive cough since 1 month.
She had been diagnosed with SLE, 7 months before and had been
taking 4 mg of methyl prednisolone three times a day.

Anamnesis

 Sepsis, HCAP, functional class IV CHF with moderate pericardial

efusion, SLE flare SLEDAI score12 with serositis, hematological
and renal involvements, acute on CKD.
Patient underwent hemodialysis and was administered
meropenem 2x500 mg, methyl prednisolone 2x62.5 mg
Sputum culture and resistance was Enterococcus sp and
Candida albicans ampicillin sulbactam 3x3 g and fluconazole
2x200 mg IV, also Mycophenolate 2x180 mg as
imunosuppresant

DIAGNOSIS
AND
TREATMENT
Radiology

Chest x-ray infiltrate on both lungs with right pleural efusion,

cardiomegaly.
ECG test result was sinus rhythm and low voltage.
Echocardiography decreased LV function with EF of 39% and
moderate pericardial efusion

2 Days in
ward

Her main symptom worsened and the fever persisted. Her

respiratory was failure and her was intubated.
Hb: 5.9 g/dl, Ht: 18.4 %, WBC: 11430/l Dif count 0/0/95,9/2/
2,1, PLT: 186000/l and PCT: 63.47 ng/ml, Anti ds DNA 684.5 .

CLINICAL QUESTION
Can procalcitonin be uses to diferentiate bacterial
infection and disease flare on patient with systemic
lupus erythematosus?

METHODS

PUBMED

COCHRANE

Procalcitonin AND Infection AND

(Systemic Lupus Erythematosus OR SLE
Flare)
12 articles
Limited articles within 2004-2014
only.
Review articles and those that were
not specific for SLE were excluded

3 articles

0 articles

CRITICAL APPRAISAL

IMPORTANCE
Variable

Wei Li Ho et al

KM Bador et al

Jinquan Yu et
al

Sensitivity

Sens: 89,5%

I. Sens SLE : 80%

Sens : 74,5%

and

Spec: 100%

Spec SLE : 78%

Spec: 95,5%

II. Sens SLE Flare : 83%

Specifity

Spec SLE : 71%

Likelihood

(+) = ~

I.

(+) = 3,6/(-) 0,2

Ratio

(-) = 0,1

II. (+)= 2,8/(-) 0,2

(+)= 16,5
(-)= 0,2

Variable

Wei Li Ho et al

KM Bador et al

Jinquan Yu et
al

Participan 49 SLE with febrile

-

ts

68 SLE

114 SLE flare patients

30 SLE flare without -

6 infected with SLE -

infection

flare

infection

19 SLE with bacterial -

4 infected SLE without -

67 without infection

infection

flare

47 with bacterial

24 non infected with

SLE flare

34 non infected SLE

without flare

Study
Design

Retrospective study

Cross sectional study

Retrospective study

Ho W-L, Lan J-L, Chen D-Y, Chen Y-H, Huang W-N, Hsieh T-Y. Procalcitonin may be a potential biomarker for distinguishing bacterial infection from disease activity in febrile patients with systemic lupus erythematosus. Formosan
Journal of Rheumatology. 2009; 23: 528.

Bador KM , Intan S, Hussin S, Gafor AH . Serum procalcitonin has negative predictive value for bacterial infection in active systemic lupus erythematosus. Lupus. 2012; 21(11): 1172 7.
Jinquan Y, Bingling X, Huang Y et al. Serum Procalcitonin and C-reactive protein for diferentiating bacterial infection from disease activity in patients with systemic lupus erythematosus.
Mod Rheumatol. 2014; 24(3): 457-63.

Variable

Wei Li Ho et al

KM Bador et al

Jinquan Yu et
al

Exclusion
Criteria

Not available

- Already on antibiotics

- Had acute myocardial

infarction,acute

With

no

activity

(SLEDAI score = 0)
-

With non bacterial

pancreatitis, thyroid or

infection

bronchial carcinoma or

and/or

a < 7 days history of

infection)

severe

mycobacterium

trauma

or

surgery

(viral
fungal

tuberculosis
infection

Interventio
n

PCT level was measured PCT level was measured

PCT was measured

or

Variable

Wei Li Ho et al

KM Bador et al

Jinquan Yu et
al

Compariso Positive cultures in SLE Positive

n

patients with infection

blood

result

from Positive culture of the

culture,

urine, blood,

urine

and

stool or other specimens sputum

in

SLE

patients

with

infection

Outcome

PCT

level

patients

in
with

SLE -

PCT level in SLE flare -

PCT level in SLE flare

and

with

with

without infection
-

Sensitivity

and -

specificity of PCT
-

and

without

and

without

infection

infection

PCT level in SLE with -

Sensitivity

and without infection

specificity of PCT

Sensitivity

Positive

and -

specificity of PCT

value

Positive

Negative

predictive -

and
predictive
predictive

RESULT

Wei Li Ho et al
study

Sensitivity (89.5%), and

Specificity (100%) of PCT
at the 0.74 ng/mL cutoff
value
Levels of serum PCT in the
bacterial infection group
(median 7.11 ng/mL, IQR 1.3842.83) were higher when
compared to the SLE disease
flare group (median 0.06
ng/mL, IQR 0.05-0.20,
p<0.001)

KM Bador et al
study

Procalcitonin was
significantly
higher in patients
SLE with
bacterial
infection
compared to
without infection
(0.19 vs 0.06
ng/ml, p=0.003)

Among infected
patients there
was no
significant
diference in PCT
(p=0.088) levels
between flare
and remission
patients

Among flare
patients only,
showed that
PCT (0.33
versus 0.08
ng/ml, p=
0.019) was
higher with
infection

SLE patients
without
infection,
PCT was higher
in those with
active disease
(p<0.001).
No correlation
between SLEDAI
score and PCT (r
=0.158, p =

A PCT cut-of value of 0.17

ng/ml sensitivity (83%)
and specificity (71%) to
detect infection in lupus flare
patients with NPV (94%) and
PPV (42%)

A cut-of value of 0.12 ng/ml

for PCT sensitivity (80%)
and specificity (78%) with
PPV (38%) and NPV (96%)

Jinquan yu et all
study

The cutoff value 0.38 ng/ml

had the best combination to
compare SLE flare with and
without infection
sensitivity (74.5%) and
specificity (95.5%), while
the PPV and NPV were
92.1% and 84.2%,
respectively

DISCUSSION

 Procalcitonin (PCT) is a 116-amino-acid residue peptide with molecular

weight of about 13 kDa
PCT was first described by Le Moullec et al. in 1984
PCT produced by the C cells of the thyroid gland as a precursor protein of
calcitonin
Synthesis and secretion during infections extra-thyroidal (the lung, liver,
pancreas, colon, and other organs)
Liliana simon et al, from the systematic reviews and meta-analysis serum PCT
and CRP as markers for bacterial infection, found that PCT level was more
sensitive (88% vs. 75%) and more specific (81%vs. 67%) than CRP level for
diferentiating bacterial from non-infective causes of inflammation.

Serum PCT is normally undetectable (< 0.05 ng/mL) PCT levels > 0.5
ng/mL are used to distinguish infections from non-infectious inflammation

Hatzistilianou M . Diagnostic and prognostic role of procalcitonin in infections. Scientific World Journal. 2010; 10: 1941 6.
Muller Beat, Kenneth L. Procalcitonin: how a hormone became a marker and mediator of sepsis. Swiss Med Wkly. 2001; 131: 595-602.
Maruna P, Nedelnikova K. Physiology and genetics of procalcitonin. Physiol. Res. 2000; 49: S57-S61.

Christ Mirjam, Muller beat. Procalcitonin in bacterial infections hype, hope, more or less?. Swiss Med Wkly. 2005; 1 3 5 : 4 5 1 4 6 0.

Ramanujam M, Davidson A. Targeting of the immune system in systemic lupus erythematosus. Expert reviews in molecular medicines. 2008; 10: 1-27.

NONINFECTIOUS CONDITIONS THAT MAY

INCREASE PCT LEVELS
Newborns (physiologically) during first days of life
Acute respiratory distress syndrome
Acute attacks of plasmodium falciparum malaria
Severe mechanical trauma
Following surgical trauma
Severe burns and heat strokes
Patients with medullary thyroid cancer, small cell cancer of the lung, carcinoid,
tumours with paraneoplastic hormone production
Treatment with interleukins, TNF-, and other drugs stimulating the release of
proinflammatory cytokines
Hatzistilianou M . Diagnostic and prognostic role of procalcitonin in infections. Scientific World Journal. 2010; 10: 1941 6.
Christ Mirjam, Muller beat. Procalcitonin in bacterial infections hype, hope, more or less?. Swiss Med Wkly. 2005; 1 3 5 : 4 5 1 4 6 0.

 Systematic reviews and meta-analysis by Jiunn-yih wu The use

of serum procalcitonin to detect bacterial infection in patients with
autoimmune disease sensitivity of 0.75 (95% CI 0.630.84) and
specificity was 0.90 (95% CI 0.850.93) compared to CRP, sensitivity

0.77 (95% CI 0.670.85) and specifity was 0.56 (95% CI 0.250.83).

The positive likelihood ratio (7.28 [95% CI 5.1010.38]) as a rule-in
diagnostic tool
The negative likelihood ratio (0.28 [95% CI 0.180.40]) low to qualify
procalcitonin as a reliable rule-out diagnostic tool

Joo K ,Park W ,Lim MJ ,Kwon SR ,Yoon J. Serum Procalcitonin for Differentiating Bacterial Infection from Disease Flares in Patients with Autoimmune Diseases. J Korean Med Sci. 2011; 26(9):
1147 51.

We Li Ho et all study Significantly higher levels of serum PCT

were noted in the bacterial infection group compared with the SLE
disease flare group a good sensitivity of 89.5% and a specificity
of 100 % serum PCT could be used as biomarker for detecting
bacterial infection in patients with SLE

KM Bador et all study negative predictive values were greater

than positive predictive values suggesting that PCT may be a
better tool to rule out infection in SLE flare patients

 Jinquan yu et al study Specifity 95,5% and positive

predictive value of PCT was up to 92.1%, indicating the
excellent ability of PCT test in diagnosing bacterial infection
in SLE Flare patients.

The result diferences may be influenced by the number of the

subject in studies, prevalence of bacterial infection case with
SLE flare, and the procalcitonin cut-of value used in the
studies

CONCLUSION

 Procalcitonin has a lower sensitivity but higher specificity with

high PPV in one study and with high NPV in the other study so can
be used to rule in or rule out bacterial infection in SLE flare
patients.
Procalcitonin can be used as a biomarker to diferentiate bacterial
infection and disease flare in patients with systemic lupus
erythematosus with cut of PCT in 0,17 ng/ml and 0,38 ng/ml.
Further prospective study with serial measurement of PCT would
present more comprehensive evidences

Thank you